We are studying methods for determining both neutrophil (N) production and destruction in neutropenic patients with various hematological and nonhematological malignancies, autoimmune states and other causes of neutropenia. We aim to develop readily available and simple methods of determining the pathophysiology of neutropenia in each case. These include a new method, based on the neutropenia, overshoot- neutrophilia cycle produced by reinfusion of cellophane-exposed blood, for determining, simultaneously, the marrow N reserves and N intravascular lifespan. This method requires no isotopes or drugs. We are continuing to investigate the standard diisopropylfluorophosphate-P32 N survival technique to establish the validity in neutropenic patients of calculating parameters of N distribution and turnover, such as the total body N pool (TBNP) and the N turnover rate (NTR). Because of the small number of circulating N, their rapid disappearance rate, and abnormal pooling in neutropenia, this technique has resulted in problems of interpretation of curves representing two or more simultaneous exponential processes. We propose specific investigations to solve these problems to establish validity of calculating TBNP and NTR in neutropenias. We are also investigating the occurrence and meaning of N-lytic antibodies in various malignant and non-malignant disorders involving autoimmunity. The overall purposes are 1) to determine how much benefit splenectomy provides to selected neutropenic patients in terms of increased resistance to drug myelotoxicity, and 2) to learn how to recognize easily the patients with whom extra caution in prescribing myelosuppressive drugs is needed to avoid potentially catastrophic N myelosuppression. Specifically, we want to determine who needs splenectomy, what changes in N physiology are produced by splenectomy, who needs steroids to eliminate anti-N antibodies, and who needs drug reduction because of occult marrow deficiency due to previous therapy.